MyD88 signaling is not essential for induction of antigen-specific B cell responses but is indispensable for protection against Streptococcus pneumoniae infection following oral vaccination with attenuated Salmonella expressing PspA antigen.
TLRs directly induce innate host defense responses, but the mechanisms of TLR-mediated adaptive immunity remain subject to debate. In this study, we clarified a role of TLR-mediated innate immunity for induction of adaptive immunity by oral vaccination with a live recombinant attenuated Salmonella enteric serovar Typhimurium vaccine (RASV) strain expressing Streptococcus pneumoniae surface protein A (PspA) Ag. Of note, oral or intranasal vaccination with RASV expressing PspA resulted in identical or even significantly higher levels of PspA-specific IgG and IgA responses in the systemic and mucosal compartments of MyD88(-/-) mice of either BALB/c or C57BL/6 background when compared with those of wild-type mice. Although PspA-specific CD4(+) T cell proliferation in the MyD88(-/-) mice was minimal, depletion of CD4(+) T cells abolished PspA-specific IgG and IgA responses in the MyD88(-/-) mice of BALB/c background. Of the greatest interest, MyD88(-/-) mice that possessed high levels of PspA-specific IgG and IgA responses but minimal levels of CD4(+) T cell responses died earlier than nonvaccinated and vaccinated wild-type mice following i.v. or intranasal challenge with virulent S. pneumoniae. Taken together, these results suggest that innate immunity activated by MyD88 signals might not be necessary for Ag-specific Ab induction in both systemic and mucosal sites but is critical for protection following oral vaccination with attenuated Salmonella expressing PspA.
Park
Sung-Moo
SM
Mucosal Immunology Section, Laboratory Science Division, International Vaccine Institute, Seoul, Korea.
Ko
Hyun-Jeong
HJ
Shim
Doo-Hee
DH
Yang
Jin-Young
JY
Park
Yong-Ho
YH
Curtiss
Roy
R
Kweon
Mi-Na
MN
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011008:Pneumococcal Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity; D051193:Toll-Like Receptors / Q000819:agonists / Q000502:physiology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D022562:Salmonella Vaccines; D051193:Toll-Like Receptors; D014613:Vaccines, Attenuated; C051592:pneumococcal surface protein A